³He MRI in mouse models of asthma

Abstract

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) 3 He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such 3 He imaging of MCh response in mice, where voxels must be ϳ3000 times smaller than in humans and 3 He diffusion becomes an impediment to resolving the airways. We show three-dimensional (

Spatially resolved assessment of serotonin‐induced bronchoconstrictive responses in the rat lung using 3He ventilation MRI under spontaneous breathing conditions

“…Mosbah et al (2) reported delayed distal lung filling following intravenous injection of methacholine in rats. Similarly, airway closures and ventilation losses were observed in mouse models of asthma, with the animals being sensitized to ovalbumin and challenged with methacholine (3,4).…”

“…A homogeneous and significant decrease of signal amplitude and maximum signal decay rate after serotonin injection was observed for each rat on the parametric color maps. The data indicate that dynamic ventilation HP 3 He MRI can be used to assess, in a spatially resolved manner, the ventilation function of spontaneously breathing rats and the effects of agents eliciting short-lasting bronchoconstriction. Magn Reson Med 63:1669-1674, 2010.…”

“…The effect on lung ventilation of bronchoconstriction induced by serotonin (intravenous injection of 50 mg/kg of serotonin) was imaged using a hyperpolarized 3 He MR ventilation protocol in spontaneously breathing rats. Lung function maps assessing airflow obstruction, a key feature in clinical pneumology, were derived from dynamic image series acquired after inhalation of 3 He gas.…”

“…Lung function maps assessing airflow obstruction, a key feature in clinical pneumology, were derived from dynamic image series acquired after inhalation of 3 He gas. Dynamic ventilation 3 He MR images spanning a respiratory cycle were obtained using a retrospective cine image reconstruction procedure. Two parameters, defined as signal amplitude and maximum signal decay rate, were derived from the time course of the MR signal for each pixel.…”

“…Hyperpolarized (HP) 3 He MRI has been previously demonstrated as a sensitive noninvasive imaging tool to study in rodents the action of bronchoconstrictive drugs such as methacholine. Chen and Johnson (1) have observed heterogeneously distributed ventilation defects following methacholine challenge in rats.…”